Plasma Exchange

  • Used to treat diseases caused by pathogenic antibodies or molecules that remain predominantly intravascular.
  • PLEX is indicated for Category I (first-line) or II (second-line) conditions, per the American Society for Apheresis Guidelines (see page 7 of ASFA Guideline 2016 attached below).
    • Category I treatments
      • Thrombotic thrombocytopaenic purpura
      • Atypical HUS
      • Acute inflammatory demyelinating polyradiculoneuropathy / Guillain-Barre syndrome
      • Acute liver failure
      • Age-related macular degeneration, dry
      • ANCA-associated rapidly-progressive glomerulonephritis
      • Anti-glomerular basement membrane disease
      • Chronic inflammatory demyelinating polyradiculoneuropathy
      • Hyperviscosity in monoclonal gammopathies
      • Liver transplatation – desensitisation for ABO incompatible living donor
      • Myasthenia gravis
      • NMDA encephalitis
      • Progressive multifocal leukoencephalopathy associated with natalizumab
      • Renal transplant
        • Antibody-mediated rejection
        • Focal segmental glomerulosclerosis recurrence in transplanted kidney
        • Desensitisation for living donor (ABO compatible or incompatible)
      • Fulminant Wilson’s disease
  • It may be used as a second- or third-line therapy for Category III condition, or, provided there is no evidence suggesting lack of benefit / harm, for a condition mediated by a pathogenic antibody where there is a theoretical and pathophysiological basis for benefit. 
  • It should not be used to treat conditions where published evidence suggests lack of benefit or harm.
  • Optimal treatment volume for each procedure is 1-1.5 plasma volumes.
    • Plasma volume calculation:
      • Plasma volume (in L) = 0.07 x weight (in kg) x (1-haematocrit)
      • Alternatively, plasma volume ≈ 40ml/kg
  • Five exchanges (to avoid excessive hypofibrinogenaemia) are typically carried out daily or on alternate days, avoiding weekends.
    • Exceptions to this are conditions such as TTP, anti-GBM disease or antibody-mediated rejection, where more intensive treatment is required.
  • Most conditions (except TTP) require only 5% albumin as the replacement fluid.
    • Albumin (compared to normal saline) maintains the patient’s whole blood viscosity and physiological albumin levels. 
    • Typically, at least 40% of the replacement fluid is given as albumin, the rest can be given as normal saline (to reduce cost and blood product exposure). However, this practice lacks published data demonstrating safety equivalence to albumin, and the incidence of vasovagal syncope may be increased. 
  • Investigations and Monitoring:
    • Before first procedure:
      • FBC (keep Hb >8 and platelet >30 – except in TTP)
      • Renal function
      • Electrolytes (especially adjusted calcium and magnesium)
      • Albumin
      • Group and screen
      • Infectious markers (HBsAg, anti-HIV, anti-HCV)
    • Before each successive procedure:
      • FBC
      • Renal function
      • Calcium, magnesium and phosphate
    • After each successive procedure:
      • Calcium, magnesium, potassium measurement
      • FBC if there was pre-existing anaemia / thrombocytopaenia, or if RBC exchange done
    • Every three procedures (if interval between procedures <3 days):
      • PT/APTT
      • Fibrinogen

TTP and Atypical HUS

  • Medical emergency requiring intensive plasma exchange (daily, including weekends).
  • Treatment should be initiated within 4hrs of presentation.
  • Replacement fluid is solvent detergent-treated FFP only, to reduce the risk of prion transmission (large volumes of exchange anticipated to exceed 50 units of FFP).
    • Rhesus D negative individuals who receive RhD positive plasma do not require RhD immune globulin for prophylaxis against immune anti-D formation.
  • Exchange volume: 1.5 plasma volumes till evidence of response, then reduce to 1 plasma volume daily.
  • Treatment duration: daily till platelet count is normal for three consecutive days.
    • In very severe cases, PLEX may occasionally be required twice daily.

Cryoglobulinaemia

  • Five exchanges initially over 2 weeks for patients with acute symptoms (e.g. digital or limb ischaemia).
  • Exchange fluid: 5% human albumin solution.
  • Exchange volume: 1 plasma volume.
  • May need to consider maintenance plasma exchange with immunosuppressive medication, particularly for p patients at ongoing risk of critical digital / limb ischaemia.

Waldenstrom’s Macroglobulinaemia

  • One to three exchanges initially, weekly to twice weekly.
  • Treatment goal: bridging till cytoreductive therapy takes effect, to reduce IgM levels prior to rituximab.
  • Exchange fluid: 5% human albumin solution.
  • Exchange volume: 1 plasma volume.
  • Patients who are refractory to chemoimmunotherapy may require maintenance plasma exchange to keep plasma viscosity less than 4.0mPa.

Risks of Plasma Exchange

  • Dilutional coagulopathy:  around 60% of coagulation factors and 85% of fibrinogen may be removed from apheresis procedures using albumin as the exchange fluid.
    • Especially dangerous if intensive PLEX performed on patients with pre-existing haemorrhagic risk (e.g. anti-GBM disease, pulmonary haemorrhage, recent renal biopsy).
    • Requires careful monitoring of fibrinogen levels during PLEX.
    • FFP may be used as part replacement fluid during PLEX (usually after every third exchange, starting with the fourth exchange).
      • E.g. for an exchange volume of 2.5L: 500ml FFP (20%) + 1L normal saline (40%) + 1L albumin (40%).
    • Alternatively, cryoprecipitate may be administered after PLEX to keep fibrinogen >1g/L.
  • Citrate toxicity: hypocalcaemia and low magnesium, with risk of neurological symptoms and arrhythmias.
    • Hypocalcaemia often causes peri-oral tingling (grade I). Grade II toxicity includes nausea and vomiting, grade III tetany, hypotension or cardiac dysrrhythmia. This can be  ameliorated by reducing the rate of citrate delivery and procedure time, and by prophylactic administration of calcium.
  • Thrombocytopaenia from platelet loss in the collected fraction.
  • Vasovagal reactions (ACE inhibitors increase this risk for all apheresis procedures, hence all patients on an ACE inhibitor should omit it 24-72 hrs before the apheresis procedure).
    • Patients who experience this should be put in a head-down position and be given 0.9% normal saline.
  • Vascular access insertion risks (if non-tunneled catheter required).
  • Blood component transfusion risks.